…

                                                                                                                  Open Peer Commentaries


the informed consent process in cancer clinical trials. Journal of        Eichenwald, K., and G. Kolata. 1999. Drug trials hide conºicts for
Clinical Oncology 14(3):984­986.                                          doctors. New York Times, 16 May.
Anonymous. 1976. Patient consent given--but forgotten. Medical            Grady, C. 2001. Money for research participation: Does it jeopar-
World News 17(4):26.                                                      dize informed consent? American Journal of Bioethics 1(2):40­44.
Appelbaum, P. S., L. H. Roth, and C. Lidz. 1982. The therapeutic          Jonsen, A. R., and J. Stryker, eds. 1993. The social impact of AIDS
misconception: Informed consent in psychiatric research. Interna-         in the United States. Washington: National Academy Press.
tional Journal of Law and Psychiatry 5:319­329.                           Minogue, B., G. Palmer-Fernandez et al. 1995. Individual autonomy
Braddock, C. H. III, S. D. Finn, W. Levinson et al. 1997. How doctors     and the double-blind controlled experiment: The case of desperate
and patients discuss routine clinical decisions: Informed decision        volunteers. Journal of Medicine and Philosophy 20:43­55.
making in the outpatient setting. Journal of General Internal Medi-       Pellegrino, E. D., and D. C. Thomasma. 1981. A philosophical basis
cine 12(6):339­345.                                                       of medical practice: Toward a philosophy and ethic of the healing
Byock, I. 1997. Dying well: Peace and possibilities at the end of life.   professions. New York: Oxford University Press.
New York: Riverhead Books.                                                U.S. Department of Health and Human Services. Ofªce of the In-
Christakis, N. 1999. Death foretold: Prophecy and prognosis in            spector General. 2000. Recruiting human subjects: Pressures in in-
medical care. Chicago: University of Chicago Press.                       dustry-sponsored clinical research. Washington: GPO.
Daugherty, C., M. J. Ratain, E. Grochowski et al. 1995. Perceptions       Yukimasa, A., K. Nakagawa, K. Hasezawa et al. 1997. Signiªcance
of cancer patients and their physicians involved in Phase I clinical      of informed consent and truthtelling for quality of life in terminal
trials. Journal of Clinical Oncology 13(5):1062­1072.                     cancer patients. Radiation Medicine 15(2):133­135.




Justice for the Professional Guinea Pig
Trudo Lemmens, University of Toronto                                      Carl Elliott, University of Minnesota



Six news items:                                                               effects, "including death" (Commons 1990, 15762­15764;
                                                                              study protocol on ªle with authors).
    In a Scottish study healthy volunteers are paid £600 pounds
    to drink orange juice laced with pesticides (Dobson 1998).                VanTx, a CRO operating in Basel, Switzerland, and with
                                                                              subsidiaries in many different countries, recruited research
    In the United States the Environmental Protection Agency                  subjects from Estonia, Poland, Macedonia, Slovakia, Peru,
    (EPA) announces that it will be considering guidelines to al-             and Ecuador to participate in Phase I and II drug trials. All
    low pesticide testing in humans. In accordance with the                   subjects are paid for their participation. Some are ºown in
    Food Quality Protection Act of 1996, the EPA must review                  from outside Switzerland. Others are asylum seekers (Hirtle,
    9,000 pesticides currently on the market to ensure that they              Lemmens, and Sprumont 2000; see also Lafraniere, Flaherty,
    meet new safety standards (Spotts 1999).                                  and Stephens 2001).
    Researchers at the National Institutes of Mental Health                   A Philadelphia 'zine for human research subjects called
    (NIMH) and elsewhere pay healthy subjects $100 to take a                  Guinea Pig Zero publishes "report cards" on a number of re-
    hallucinogenic drug called ketamine. Ketamine is ordinarily               search laboratories. Bob Helms, its publisher, gives high
    used as an animal tranquilizer, but it has also gained notori-            marks to several laboratories but criticizes others severely.
    ety as a street drug. Because of the alleged use of ketamine              He writes of incompetent venipuncturists, surly doctors and
    for date rape, several states have made possession of it a fel-           nurses, last-minute cancellations, and a patient in one study
    ony. The purpose of the NIMH studies is to induce a tempo-                who "emerged with $7,000 in his pocket and his mind on
    rary psychotic state. Researchers argue that the studies may              planet Zork." Harper's Magazine reprints several of Guinea
    offer new insights into the treatment of schizophrenia (Kong              Pig Zero's report cards. Both Harper's and Guinea Pig Zero are
    1998).                                                                    promptly sued by one of the criticized institutions. Harper's
    Opposition parties in Canadian Parliament raise questions                 prints an apology and a retraction (Weiss 1997; see also
    about the collaboration of the army in vaccination trials to              Guinea Pig Zero 1996).
    protect soldiers against chemical agents during the Gulf
    War. A contract is revealed showing that a private contract               Should we be worried that healthy people are being
    research organization (CRO) has conducted these trials on             paid to enroll in research studies? Bioethicists cannot de-
    healthy volunteers, offering Can$1400 for participation. The          cide and so the issue has dropped into a regulatory vac-
    consent form raises the spectrum of a host of potential side          uum. U.S. and Canadian regulations and guidelines frown


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The American Journal of Bioethics


on paying research subjects, but they do not prohibit it.       have argued that research studies on healthy subjects--un-
They allow researchers to pay subjects, but discourage          like research on sick patients--are best characterized as a
them from paying very much, lest subjects be "unduly            kind of labor relation (Lemmens and Elliott 1999). If reg-
inºuenced" or "coerced" into enrolling in a study against       ulatory bodies realized this, they would be in a far better
their better judgment (this basic approach can be seen in       position to protect these subjects from exploitation. Labor-
Royal College of Physicians 1986; Medical Research              type legislation could give research agencies the clout of
Council 1998; National Health and Medical Research              occupational health and safety agencies by giving them
Council of Australia 1992; Department of Health and Hu-         the power to conduct inspections and ensure that "work-
man Services 1993). Some guidelines or statutes suggest         ing" conditions are safe. Collective negotiations and
that "compensation for loss and inconvenience is accept-        unionization could give research participants a stronger
able," but other payment is not (for example, see the Que-      voice in arguing for good working conditions. Research
bec Civil Code Article 25 (2)). Given this sort of wafºing,     participants could negotiate standards of payment based
it is no wonder that Institutional Review Boards (IRBs)         on the level of discomfort they are asked to undergo, the
are bafºed. How much are researchers allowed to pay a re-       number and types of procedures, the duration of the stud-
search subject undergoing a bronchoscopy? How much for          ies, and other factors. As with worker compensation
a simple blood drawing? What is it worth to go without          schemes, research sponsors could offer appropriate com-
sleep for 36 hours, or to be exposed to malaria, or to try an   pensation schemes to provide some form of ªnancial secu-
experimental antipsychotic drug?                                rity in case participants are harmed in research studies.
     In the world that regulatory bodies have created,              Are there dangers to this kind of shift? Yes, absolutely.
healthy subjects take part in studies because of the money,     The most serious danger is that the payment argument
yet researchers have to pretend that the subjects are moti-     could be hijacked to defend even more commercialization
vated by something other than money. Research subjects          of the research enterprise and even more exploitation of
cannot negotiate payment, since payment is not supposed         vulnerable subjects. Research participants could be placed
to be the focus of the transaction. Local research ethics       at even greater risk of exploitation if limitations on pay-
boards are expected not to determine what is fair, but what     ment are simply lifted without signiªcant regulatory over-
is "undue inducement." Even worse, they must determine          haul. Guinea Pig Zero notwithstanding, research partici-
this on a case-by-case basis. Thus, if the research popula-     pants are not yet organized sufªciently to obtain better
tion is very poor, IRBs can plausibly conclude that pay-        working relations through negotiations and labor pressure
ment must be kept very low, so as not to unduly induce          tactics. And since participating in research studies cur-
subjects into enrolling. But if the research population is      rently does not count as "employment," research partici-
wealthy, subjects can be paid much more.                        pants do not even qualify for the resources and protection
     If you are a hammer everything looks like a nail; and if   provided by labor legislation. When research subjects
you are a North American bioethicist, everything looks          from Eastern Europe and South America were brought to
like a problem of informed consent. But the matter of pay-      Switzerland, their only goal was to make money. Yet their
ing healthy subjects to enroll in research studies is not       work did not fall under any category of labor. Immigration
merely a problem of informed consent. It is a problem of        and labor authorities did not deal with the issue as a mat-
exploitation. Like it or not, research on healthy subjects      ter of immigration law. Occupational health and safety
has become a commercial transaction. Volunteers gener-          regulations did not protect the research participants, nor
ally take part in research studies not for humanitarian mo-     did employment regulations. Thus the issue was left in the
tives, but for the money. The studies they take part in are     hands of Swiss health authorities, who acted only after the
often funded or conducted by pharmaceutical companies           media became involved in the case.
or other large corporate bodies. In many cities these proto-        It would also be a mistake to force all research partici-
cols take place in CROs--for-proªt bodies often set up          pants, sick and healthy, into the same regulatory box.
solely for the purpose of conducting research, mostly on        Dickert and Grady have argued in the New England Journal
healthy volunteers. Unlike patients, healthy volunteers         of Medicine that "(t)here is no inherent reason to treat pa-
have no personal stake in the illnesses to which the re-        tients and healthy subjects differently with respect to pay-
search might be applied. They typically volunteer in re-        ment" (1999). But patients are in situations fundamen-
sponse to advertisements in the newspapers or on the            tally different from those of healthy volunteers. Often they
Internet.                                                       are vulnerable because of their illnesses. They are fre-
     It is time to stop pretending that the relationship be-    quently asked to accept signiªcant risks by foregoing stan-
tween for-proªt, multibillion-dollar corporate entities and     dard treatment and accepting experimental treatment.
healthy volunteers is the same as the relationship between      They may have a sense of obligation toward the physician-
an academic physician-investigator and sick patients. We        investigator or to an institution that has provided them


52 ajob                                                                                        Spring 2001, Volume 1, Number 2
                                                                                                        Open Peer Commentaries


with care in the past. To import commercial consider-           Dickert, N., and C. Grady. 1999. What's the price of a research sub-
ations into this already fragile relationship would be to       ject? Approaches to payment for research participation. New Eng-
court the risk of serious exploitation.                         land Journal of Medicine 341(3):198­203.

    There are other dangers in introducing payment with-        Dobson, R. 1998. Boom in drug tests on humans. The Independ-
out signiªcant regulatory changes. First, if market mecha-      ent, 2 August.
nisms are introduced without well-constructed limita-           Guinea Pig Zero: A Journal for Human Research Subjects. 1996.
tions, noncommercial research sponsors could ªnd                2 August.

themselves facing problems recruiting study participants.       Hirtle, M., T. Lemmens, and D. Sprumont. 2000. A comparative
Second, efforts to compensate participants fairly according     analysis of research ethics review mechanisms and the ICH GCP
                                                                Good Clinical Practice Guideline. European Journal of Health Law
to local market standards may be undermined as research
                                                                7:75­102.
moves beyond national borders. Third, payment could cre-
                                                                Kong, D. 1998. Drug studies are questioned. The Boston Globe, 31
ate problems with subject selection and the generaliza-
                                                                December.
bility of research ªndings by attracting a limited, unrepre-
                                                                Lafraniere, S., M. P. Flaherty, and J. Stephens. 2000. The body
sentative population of participants. However, this risk
                                                                hunters part 3: Submit or suffer: "Uninformed consent" is raising
may be minimal in many clinical trials involving healthy
                                                                ethic of drug test boom. Washington Post, 19 December.
volunteers, which are often of little scientiªc value and are
                                                                Lemmens, T., and C. Elliott. 1999. Guinea pigs on the payroll: The
conducted simply to fulªll regulatory testing require-
                                                                ethics of paying research subjects. Accountability in Research 7(1):
ments for "me-too" drugs.                                       3­20.
    The current regulatory system is even more dangerous.
                                                                Medical Research Council. Natural Sciences and Engineering
Ethical guidelines and regulations ought to protect             Council and Social Sciences and Humanities Research Council of
healthy research subjects from exploitation. But instead,       Canada. 1998. Tri-council policy statement on ethical conduct for
the current regulatory scheme prohibits subjects from re-       research involving humans.
ceiving a fair wage and denies them the legal resources         National Health and Medical Research Council of Australia. 1992.
available to other high-risk workers. As the lawsuit            Statement on human experimentation.
against Guinea Pig Zero showed, research participants are       Royal College of Physicians. 1986. Research on healthy volunteers.
virtually powerless in their dealings with the multi-billion    A report of the Royal College of Physicians. Journal of the Royal
dollar biomedical research industry. Labor legislation, in      College of Physicians of London 20(4):243­257.
contrast, would reºect the recognition that healthy re-         Spotts, P. 1999. How ethical is testing pesticides on people, EPA
search subjects volunteer because they are in ªnancial          asks. The Christian Science Monitor, 14 January.
need, and that ªnancial need is the locus of their vulnera-     U.S. Department of Health and Human Services. Ofªce of Protec-
bility. I                                                       tion from Research Risks. 1993. Protecting human research sub-
                                                                jects: IRB guidebook. Washington: GPO.
References                                                      Weiss, R. 1997. Hospital demands Harper's halt distribution of July
Canada. House of Commons. Debates, 22 Nov. 1990­18 Dec. 1990.   issue. Washington Post, 18 June.




Treating Research Subjects as Unskilled Wage Earners:
A Risky Business
Nancy King Reame, University of Michigan



As a women's health researcher, I routinely compensate          subjects undergo treatment with hormones or drugs, EEG
volunteers who participate in my clinical studies (Reame        monitoring for sleep assessment, and other invasive or po-
2001). Like Christine Grady (2001), I think it would be         tentially embarrassing procedures such as pelvic exams.
wrong to not do otherwise, given the time demands, level        Sometimes they must return three or four times at weekly
of inconvenience, and potential risks. Our protocols in-        intervals to repeat the protocol. Most contribute approxi-
volve an overnight stay in the university hospital's clinical   mately 36 hours of their time. Depending on the goal of
research center, during which time blood is sampled every       the experiment, volunteers for these tedious, labor-inten-
ten minutes through an IV line for 24 hours. Sometimes          sive studies include college students, patients, hospital



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